Conventionally, a microneedle device is known as a device for enhancing transdermal drug absorption. The microneedles of a microneedle device aims to puncture the outermost layer of the epidermis, the corneum, and various sizes and shapes are proposed in the hope of a noninvasive administration method (e.g., Patent Document 1).
Similarly, various drug application methods using a microneedle device are proposed. Known examples include that a drug is coated on a microneedle surface; a groove or hollow is provided in a microneedle to allow a drug or a biological component to penetrate therethrough, a microneedle itself is mixed with a drug, etc. (e.g., Patent Document 2).
Thus, as a way of effectively facilitating transdermal drug absorption using a microneedle device, there is a method by which a drug is coated on a part of the surface of a microneedle device. In particular, when a drug is coated on a part of a microneedle device (especially only on microneedles), all or most of an applied drug is delivered into the body and hence such a method is useful as a very efficient and accurate administration method.
Further, since these proposed microneedle devices are all provided with extremely small protrusions having a height of about several tens to several hundreds micrometers, it can be easily assumed that a transdermal drug absorption and efficiency greatly vary depending on drug applications.
Patent Document 3 discloses a microdroplet coating method using the ink jet method, etc., by which droplets are selectively released to only microneedles.
However, the document does not describe a method by which only a part (microneedles) of a microneedle device is coated by precise position control and release control. In the typical ink jet methods, the releasable amount is a picoliter order, thereby limiting an amount coatable at a time. Further, the viscosity of a coating solution is limited to the lower side (<50 cps). For this reason, it is thought to be difficult to selectively coat only microneedles in a highly reproducible manner.
Patent Document 4 discloses a method of selectively coating only the tip of a microneedle with a solution containing a drug. More specifically, the method controls the level of a drug to be coated by immersing a microneedle in the coating solution controlled at a given depth. The depth of a coating solution is controlled using a cylindrical roller and the liquid viscosity of the solution is limited to about 500 cps or lower, thereby achieving a quantitative coating. This method enables the selective coating of a drug only to microneedles and is hence considered useful as a method of coating a drug quantitatively. However, since the viscosity range of a coating solution is limited to a low viscosity range (about 500 cps or lower), a drug amount coated by a single immersion is limited to a certain extent. As a result, when a coated amount must be controlled, particularly when a large amount of drug needs to be coated, the immersion-drying cycle must be inevitably repeated a number of times.
When the operation of shifting a coating solution by rolling using a cylinder is repeated, the concentration of the coating solution is liable to increase gradually. Further, when an attempt is made to coat a drug only on an microneedle by this method, it is quite predictable that the capillary phenomenon occurs depending on the surface tension of a coating solution used, causing the wicking phenomenon wherein the solution extends to the basal surface (root portion) of microneedle or to the bottom of microneedle substrate.
Patent Document 5 discloses a coating method using a removable mask phase. In this method, using phase-separable solvents having different volatilities as masking materials, a physiologically active substance is coated on the tip of a microneedle by volatilizing the solvents step by step. This method enables the drug coating only on a microneedle, but it is expected that the drying step requires some time depending on drugs and the residual mask phase on the microneedle is also concerned.
Patent Document 6 discloses a coating method of coating needles on the microneedle substrate and developed based on the dip coating method. This method employs a mask (physical mask) having apertures formed thereon corresponding to the pitch of microneedles in order to prevent the wicking phenomenon caused by the surface tension of a coating solution from occurring, and controls the coating amount by controlling the surface position of the coating solution and the contact level of microneedles. However, in this method, since the reservoir storing the coating solution is directly connected to the mask apertures in which the microneedles are inserted, the level of coating amount is liable to vary significantly depending on the position of inserting the needles. Even when the insertion level is strictly controlled, it is essential to maintain the balance between the surface tension of coating solution and the surface energy of needles. When this balance is lost, the coating level and amount to the microneedles may change. Further, the coating solution level with respect to the mask surface must be strictly controlled which requires a power unit to always maintain the solution at a constant level.    Patent Document 1: National Publication of International Patent Application No. 2001-506904    Patent Document 2: National Publication of International Patent Application No. 2004-504120    Patent Document 3: National Publication of International Patent Application No. 2004-520152    Patent Document 4: WO02/074173A1    Patent Document 5: WO2006/055799A1    Patent Document 6: WO2006/138719A2